Method and apparatus for inducing sputum samples for diagnostic evaluation

ABSTRACT

An apparatus for inducing sputum samples for diagnosing pulmonary disorders, especially as it relates to detection of early stages of lung cancer. The apparatus is comprised of a pneumatic chest compression vest, a pneumatic pressure generator, and a mouthpiece connected to a nebulizer. Sputum samples are induced by applying an oscillating force to the chest via the pneumatic chest compression vest and pressure generator, while simultaneously providing an aerosolized solution (such as normal or hypertonic saline) via the nebulizer while the patient is standing. The sample is subsequently evaluated to ascertain a patient&#39;s risk of or the presence of a pulmonary disorder such as lung cancer.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is related to “Chest Compression Vest with Front PanelBib” and “Chest Compression Vest with Connecting Belt”, which were filedon the same day and also assigned to American Biosystems.

BACKGROUND OF THE INVENTION

The present invention relates to an apparatus and method for inducingsputum samples from a patient. In particular, the present inventionrelates to obtaining high quality sputum samples for diagnosingpulmonary disorders, especially lung cancer.

Lung cancer has a survival rate of only 14% and is the leading cause ofcancer death in the United States. The poor prognosis for lung cancer isrelated to both the lack of effective early detection methods, and theinability to precisely locate the diseased area of the lung to betreated. However, improved imaging techniques now allow much bettertumor location capabilities, once detected, to allow specific treatmenteven at very early stages.

A cooperative trial undertaken by Johns Hopkins Oncology Center,Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic utilizedsputum induction as an early screening method to determine if areduction in lung cancer deaths could be achieved. This study showed theresectability and survival rates among the study group were higher thanamong the control group, but the mortality rates were not reduced. Thisresult led health policy groups to conclude that this type of screeningmethod could not be justified.

These findings discouraged further research using sputum cytology forearly cancer detection. Recent findings in lung tumor biology researchrenewed interest in the use of noninvasive techniques for screening.Biomarkers which indicate phenotypic and genotypic abnormalities andtrack the transformation of bronchial epithelium into a malignant tumorhave been found. Sputum samples are prime candidates for diagnosingcancer with biomarkers, because it is believed that exfoliatedepithelial cells recovered in sputum samples may provide the earliestindicators of lung cancer. A number of molecular genetic techniques haveprovided evidence that biomarkers can be detected in sputum.

Studies utilizing computer assisted, high-resolution image analysis havedetected changes associated with cell transformation in normal appearingsputum samples, and also squamous cell carcinomas were detected inotherwise normal appearing epithelial cells. In addition, a number ofmonoclonal antibodies have been used to detect tumor-associated surfaceantigens on bronchial epithelial cells prior to the development of apulmonary neoplasm. These types of studies strongly indicated thatsputum cytology had the potential to improve the sensitivity,specificity, and predictive value for early diagnostic screening.

The major flaw with these methods was that repeat samplings wererequired to ensure adequate samples for analysis which is costly andjeopardizes a timely diagnosis. Two methods have commonly been used tocollect sputum. One method uses ultrasonic nebulizer treatments toprovide a mild bronchial irritant which induces a cough and suppliesmoisture to facilitate mucus passage. The other method is an earlymorning cough technique to collect samples. Four independent studieswere performed which utilized the two collection methods and tried todetermine whether either or both would be adequate and, therefore,useful for early diagnostic screenings. The results, however, wereinconclusive.

Thus, a new method is needed to produce reliable samples whileminimizing repeat sampling. This method could also be utilized toevaluate other pulmonary disorders and diseases such as asthma, chronicobstructive pulmonary disease (COPD), tuberculosis, Pneumocystis cariniipneumonia (PCP), inflammation, and infection by morphologic,immunochemical, fluorescence, molecular, or genetic techniques.

A vest apparatus has been used by clinicians to facilitate mucus passagefor patients with pulmonary disorders. The most widely used device isthe ABI Vest Airway Clearance System by American Biosystems, theassignee of the present application. The apparatus compresses the chestat an alternating frequency faster than breathing which increasesairflow velocity, creates cough-like shear forces, decreases theviscosity of mucus, and increases mucus mobilization. This apparatus,until now, has only been used therapeutically for patients with problemssuch as cystic fibrosis and asthma.

BRIEF SUMMARY OF THE INVENTION

The invention discloses a method for inducing sputum from a patient, anapparatus for inducing and collecting those samples from the patient,and a method of evaluating patients for pulmonary disorders utilizingthe sputum samples. The method of inducing the sputum sample includesapplying an oscillating force to the chest of the patient whilesimultaneously providing the patient with a mouthpiece to maximizeairflow velocity. In the preferred embodiment, the patient will bemaintained in a standing position and also provided with a nebulizerthat is connected via a port to the mouthpiece. The nebulizer producesan aerosolized solution, possibly a mild bronchial irritant, for thepatient to inhale. In addition, the oscillating force is selected tomaintain peak airflow velocities throughout the process.

The method of screening patients for pulmonary disorders includescollecting a sputum sample which is induced by the oscillating force andthe increased airflow velocity. The sample is subsequently analyzed andthe patient is assessed as to the presence of or the risk of a pulmonarydisorder, for example lung cancer. The apparatus for inducing the sputumsample from a patient includes a pneumatic chest compression vest andpneumatic pressure generator to provide the oscillating force to thechest of the patient, and a mouthpiece placed in the patient's mouth. Inthe preferred embodiment, a source of nebulized solution is coupled tothe mouthpiece, and a support is also provided to maintain the patientin a standing position. In addition, the pneumatic chest compressionvest is positioned and the parameters optimized in order to maintainpeak airflow velocities. Intermittently during an approximate 12 minutetreatment, the treatment is stopped, and the patient expectorates theinduced sputum into sampling containers.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a person using the preferred embodiment ofthe apparatus.

FIG. 2 is an illustration of a person fitted with a chest compressionapparatus.

FIG. 3 is an illustration of a person with a mouthpiece coupled to anebulizer for providing an aerosolized solution.

FIG. 4 is an illustration of a person and a standing support.

FIG. 5 is an illustration of a standing support.

DETAILED DESCRIPTION

FIG. 1 is an illustration of person 10 undergoing treatment using thepresent process and apparatus. The apparatus includes pneumatic chestcompression vest 12, pneumatic pressure generator 14, hoses 16,mouthpiece 18 with nebulizer 20 and air supply tube 22, and standingsupport 24.

Pneumatic chest compression vest 12 is worn around the upper torso ofperson 10. Pneumatic pressure generator 14 is connected to pneumaticchest compression vest 12 by hoses 16. Person 10 holds mouthpiece 18 inhis or her mouth. Mouthpiece 18 is connected to nebulizer 20 which issupplied air by air supply tube 22 (which is connected to an air supplythat is not shown). In a preferred embodiment, person 10 is kept in astanding position by standing support 24.

In operation, pneumatic pressure generator 14 maintains a positivepressure bias and delivers oscillated pneumatic pressure through hoses16 to pneumatic chest compression vest 12, which produces oscillatingchest compressions on the chest of person 10 Simultaneously, amouthpiece is held in the mouth of person 10. In a preferred embodiment,a solution, such as a mild bronchial irritant, contained in nebulizer 20is inhaled by person 10. Nebulizer 20 is connected to mouthpiece 18.Mouthpiece 18 maintains the airways open to maximize airflow velocitiesand minimizes the amount of aerosolized solution lost in the air duringtreatment.

The process and apparatus move the mucus, which contains the treatment.The treatment is stopped, person 10 removes mouthpiece 18, coughs, andcollects sputum in a cup (not shown) that is provided. Treatment is thenresumed. The sputum sample is subsequently evaluated as to risk of orthe presence of pulmonary disorders such as lung cancer. The combinationof mouthpiece 18 with nebulizer 20 and chest compressions while in astanding position provides an optimal method for obtaining qualitysputum samples.

FIG. 2 is an illustration of person 10 wearing pneumatic chestcompression vest 12. This illustration demonstrates how person 10 havingtorso T, rib cage R, and collar bones C, is fitted into pneumatic chestcompression vest 12. Pneumatic chest compression vest 12 is composed ofan inelastic, flexible shell 30 (which has front panel section 32 andwrap-around belt section 34), flexible liner 36 (shown in phantom)attached to the inner surface of front panel section 32 to form aflexible air bladder, suspenders 38, and air couplings 40. A preferredembodiment of pneumatic chest compression vest 12 is described in detailin the previously mentioned related applications, which are incorporatedby reference.

Front panel section 32 is shaped to cover the person's chest from thebottom of rib cage R to near collar bones C, the region of the person'schest that encompasses the lungs. Front panel section 32 has central bibportion 32A which is about 11.75 inches in height, but can range fromabout 9.0 inches to about 13.0 inches, and a pair of side portions 32Band 32C which are about 7.25 inches in height but can range from about6.0 inches to about 9.0 inches. The width of front panel section 32 isabout 21 inches. Side portions 32B and 32C allow front panel section 32to extend under the person's arms. Preferably, these sections are madefrom 8 mil polycarbonate plastic which reduces stretching.

Flexible liner 36 covers essentially all of the inner surface of frontpanel section 32 and is sealed around its edges to front panel section32. The flexible liner 36 is preferably made from 4 mil polyethylene.Together, front panel section 32 and flexible liner 36 define an airbladder which is inflated against the person's chest to applycompressive force to the chest and lungs. The compressions are focusedon the region of the chest that encompasses the lungs, which effectivelymoves mucus from all lobes of the lungs. Air is supplied to the airbladder through a pair of ports in front panel section 32 into which aircouplings 40 are inserted. Hoses 16 connect pneumatic pressure generator14 to air couplings 40 and to the air bladder formed by front panelsection 32 and flexible liner 36.

Belt section 34 is attached to side section 32B of front panel 32 and islong enough to wrap around torso T of person 10 and extend across theother side section 32C and bib section 32A. Belt section 34 has a seriesof longitudinally spaced belt holes 42 extending along its length. Asshown in FIG. 2, two of the belt holes 42 are aligned with the ports offront panel section 32 so that air couplings 40 are inserted into beltholes 42 and into the air ports. As a result, belt section 34 is held inplace around torso T and is connected to bib section 32A by aircouplings 40. Other belt holes 42 on belt section 34 are used forattachment of suspenders 38.

In one embodiment, belt section 34 has a height of about 7.25 inches anda length (in the horizontal direction) of about 42 inches. Belt holes 42are about 1.4 inches in diameter and are spaced on about 2 inch centers.Depending on the circumference of the person's chest, belt section 34will wrap around the chest so that different belt holes 42 will bealigned with the air ports of front panel section 32. This allowspneumatic chest compression vest 12 to fit securely around person 10.

Pneumatic pressure generator 14 produces oscillatory pneumatic pressureand a positive pressure bias which is delivered through hoses 16 to theair bladder defined by front panel section 32 and liner 36. In oneembodiment, the oscillatory pneumatic pressure that is delivered to theair bladder is at a frequency of between about 5 and about 25 pressurecycles per second. The oscillatory frequency preferably ranges betweenabout 12 and about 15 pressure cycles per second, with the preferredfrequency being approximately the chest resonant frequency. The forcecreated on the chest of person 10 compresses a bronchial airwayslightly. The force on the mucus (F) is related to a diameter of theairway (d) by the following equation, F=1/d⁴. Therefore, even a slightnarrowing of the airway, as caused by pneumatic chest compression vest12, causes the force on the mucus during the outflow portion of theoscillation to increase as the fourth power of the diameter reduction.During the inflow portion of the oscillation, the airway is notcompressed, and therefore, the force on the mucus is less. This resultsin the mucus being pushed up and out of the airway more than it ispushed back down the airway.

The positive pressure bias that is provided to pneumatic chestcompression vest 12 is about 7 inches of water (0.25 P.S.I. or 13 mmHg).The pressure compresses the chest to create an outward airflow biaswhich creates the force to move the mucus. The pressure setting andfrequency of force are selected for a maximum airflow velocity ofgreater than about 50 ml/cycle while maintaining comfort. This, in turn,maximizes the force on the mucus to increase mobilization.

Ideally, the treatment lasts for about 12 minutes but can last as longas about 20 minutes. A timer stops the treatment once it reaches about12 minutes, but it can be restarted.

The apparatus also includes mouthpiece 18 which is illustrated in FIG.3. This illustration demonstrates how mouthpiece 18 is used and hownebulizer 20 is connected to it. FIG. 3 shows person 10 with mouth M,mouthpiece 18, nebulizer 20, nebulizer port 50, and air supply tube 22.

The mouthpiece 18 extends into mouth M of person 10. Nebulizer 20 iscoupled to mouthpiece 18 via nebulizer port 50. Nebulizer 20 isconnected to an air supply via air supply tube 22.

In operation, the air supply provides a low airflow to nebulizer 20through air supply tube 22. The airflow aerosolizes a solution, such asa mild bronchial irritant like hypertonic saline, contained in nebulizer20 and allows person 10 to inhale the solution. The solution providesmoisture to facilitate mucus mobilization, and some solutions may alsohelp induce a cough.

Mouthpiece 18 extends about 1.5 inches into mouth M and holds open mouthM while depressing the tongue of person 10 to maximize airflow velocity.Preferably, mouthpiece 18 has an 8 inch long, 1 inch diameter extensionoutside mouth M beyond nebulizer 20, which limits the amount ofaerosolized solution lost to the room during treatment. In a preferredembodiment, mouthpiece 18 is PVC plastic and has a generally ovalcross-section and is about 1.5 inches wide by about 0.6 inches high.This size permits an airflow velocity of about 90 ml/cycle during thetreatment.

In order to maximize inducement of sputum, person 10 should be kept in astanding position. FIG. 4 illustrates person 10 with feet F, legs L, andhands H using standing support 24. This figure shows how person 10 ispositioned on standing support 24. As shown in FIGS. 4 and 5, standingsupport 24 includes seat 60, telescoping support 62, handlebars 64,height adjustment means 66, and platform 68.

Person 10 leans against seat 60. Feet F of person 10 rest on platform68. Hands H of person 10 grip handlebars 64. Seat 60 sits on top of andis connected to support 62. Handlebars 64 are connected near the top ofsupport 62. Support 62 rests on top of and is connected to the center ofplatform 68. Height adjustment means 66 is on support 62, and permitstelescoping adjustment of the height of support 62 and then lockssupport 62 at the adjusted height. Any known height adjustmentstructure, such as those commonly used to adjust chair heights, can beused.

In operation, person 10 is positioned against standing support 24 asdescribed above. Height adjustment means 66 is set so that legs L ofperson 10 are straight. This maintains person 10 comfortably in astanding position which is the most effective body position for thetreatment, because it produces the highest airflow velocities.

Once a sputum sample has been collected using the present method andapparatus, the sample is prepared for cytological evaluation, thenanalyzed and assessed. In one embodiment, a sample can be assessed as toa person's risk for lung cancer.

The evaluation can also include other pulmonary disorders and diseases,such as asthma, COPD, tuberculosis, PCP, inflamation and infection,which can be diagnosed using morphologic, immunochemical, fluorescence,molecular, or genetic techniques.

Although the present invention has been described with reference topreferred embodiments, workers skilled in the art will recognize thatchanges may be made in form and detail without departing from the spiritand scope of the invention.

What is claimed is:
 1. A method of inducing sputum samples from apatient, the method comprising: applying an oscillating force to a chestregion of the patient; and supplying a mouthpiece for the patient tobreathe through while applying the oscillating force.
 2. The method ofclaim 1 and further comprising: maintaining the patient in a generallystanding position while applying the oscillating force.
 3. The method ofclaim 2 wherein maintaining the patient in a generally standing positioncomprises positioning the patient on a standing support.
 4. The methodof claim 1 wherein the oscillating force is applied at a frequency andpositive pressure bias to produce an average peak airflow velocity fromthe patient of greater than about 50 ml/cycle.
 5. The method of claim 4wherein the oscillating force is applied at a frequency which isapproximately a chest resonant frequency of the patient.
 6. The methodof claim 5 wherein the frequency of the oscillating force is betweenabout 12 pressure cycles per second and about 15 pressure cycles persecond.
 7. The method of claim 4 wherein the positive pressure bias isabout 7 inches of water (0.25 P.S.I or 13 mmHg).
 8. The method of claim1 wherein the oscillating force is applied at a frequency of betweenabout 5 pressure cycles per second and about 25 pressure cycles persecond.
 9. The method of claim 1 wherein applying an oscillating forceis for a time period up to about 20 minutes.
 10. The method of claim 1wherein applying an oscillating force comprises: positioning aninflatable chest compression vest around the patient's chest; andsupplying an oscillating air pressure to the vest.
 11. The method ofclaim 10 wherein the vest is positioned with a lower edge near a bottomof the patient's rib cage and with an upper edge near the patient'scollar bones.
 12. The method of claim 1 and further comprising:supplying a nebulized solution for the patient to inhale while applyingthe oscillating force.
 13. The method of claim 12 wherein supplying anebulized solution is through the mouthpiece.
 14. The method of claim 12wherein the nebulized solution is a mild bronchial irritant.
 15. Themethod of claim 1 wherein the mouthpiece extends into the patient'smouth to hold the patient's tongue depressed.
 16. The method of claim 1wherein the mouthpiece is sized to permit airflow velocities of greaterthan about 50 ml/cycle while applying the oscillating force.
 17. Themethod of claim 1 and further comprising: interrupting the applying ofthe oscillating force to permit the patient to expectorate inducedsputum into a sampling container.
 18. An apparatus for inducing sputumsamples from a patient, the apparatus comprising: a chest compressionvest for applying force to a chest region of the patient; a pressuregenerator connected to the vest for providing an oscillating pressure;and a mouthpiece, having a passageway of substantially uniformcross-sectional area between opposite open ends, for placement in thepatient's mouth to minimize airflow resistance, the mouthpiece beingremovable to permit the patient to expectorate an induced sputum sample.19. The apparatus of claim 18 and further comprising: a support whichmaintains the patient in a generally standing position.
 20. Theapparatus of claim 18 wherein the pressure generator provides theoscillating pressure at a frequency of between about 5 and about 25pressure cycles per second.
 21. The apparatus of claim 20 wherein theoscillating pressure has a frequency which is approximately a chestresonant frequency of the patient.
 22. The apparatus of claim 20 whereinthe oscillating pressure has a frequency between about 12 pressurecycles per second and about 15 pressure cycles per second.
 23. Theapparatus of claim 20 wherein the pressure generator provides a positivepressure bias to the vest of about 7 inches of water (0.25 P.S.I. or 13mmHg).
 24. The apparatus of claim 18 wherein the vest has a lower edgefor positioning near a bottom of the patient's rib cage and an upperedge for positioning near the patient's collar bones.
 25. The apparatusof claim 18 wherein the mouthpiece extends into the patient's mouth tohold open the patient's mouth and depress the patient's tongue.
 26. Theapparatus of claim 18 wherein the mouthpiece has a generally ovalcross-section.
 27. The apparatus of claim 26 wherein the mouthpiece isabout 1.5 inches wide, about 0.6 inches high and extends about 1.5inches into the patient's mouth.
 28. The apparatus of claim 18 andfurther comprising: a port on the mouthpiece for connection to a sourceof a nebulized solution.
 29. A method of noninvasively producing samplesfrom patients for evaluation of pulmonary disorders, the methodcomprising: applying an oscillating force to a chest of a patient;supplying a mouthpiece for the patient to breathe through; andcollecting a sputum sample from the patient which is induced by theoscillating force and the mouthpiece.
 30. The method of claim 29 andfurther comprising: supplying a nebulized solution for the patient toinhale while applying the oscillating force.
 31. The method of claim 29and further comprising: providing assessment following cytologicalevaluation of the sputum sample to determine the presence of or thepatient's risk for a pulmonary disorder.
 32. The method of claim 31wherein the patient is classified as to risk of lung cancer based uponthe assessment.
 33. An apparatus for inducing sputum samples from apatient, the apparatus comprising: a chest compression vest for applyingforce to a chest region of the patient; a pressure generator connectedto the vest for providing an oscillating pressure; a mouthpiece forplacement in the patient's mouth; and a support which maintains thepatient in a generally standing position.
 34. An apparatus for inducingsputum samples from a patient, the apparatus comprising: a chestcompression vest for applying force to a chest region of the patient; apressure generator connected to the vest for providing an oscillatingpressure at a frequency between about 5 and about 25 pressure cycles persecond, which is approximately a chest resonant frequency of thepatient; and a mouthpiece for placement in the patient's mouth.
 35. Anapparatus for inducing sputum samples from a patient, the apparatuscomprising: a chest compression vest for applying force to a chestregion of the patient; a pressure generator connected to the vest forproviding an oscillating pressure at a frequency between about 5 andabout 25 pressure cycles per second and a positive pressure bias to thevest of about 7 inches of water (0.25 P.S.I. or 13 mmHg); and amouthpiece for placement in the patient's mouth.
 36. An apparatus forinducing sputum samples from a patient, the apparatus comprising: achest compression vest for applying force to a chest region of thepatient; a pressure generator connected to the vest for providing anoscillating pressure; a mouthpiece, having a passageway of substantiallyuniform cross-sectional area between opposite open ends, for placementin the patient's mouth to minimize airflow resistance; and a port on themouthpiece for connection to a source of a nebulized solution.
 37. Anapparatus for inducing sputum samples from a patient, the apparatuscomprising: a chest compression vest for applying force to a chestregion of the patient; a pressure generator connected to the vest forproviding an oscillating pressure; and a mouthpiece, having a passagewayof substantially uniform cross-sectional area between opposite openends, having a first portion for holding open the patient's mouth whiledepressing the patient's tongue, and having a second portion forlocation outside the patient's mouth, the second portion having a portfor receiving an aerosolized solution.
 38. The apparatus of claim 37wherein the first portion of the mouthpiece has a generally ovalcross-section.
 39. The apparatus of claim 38 wherein the first portionof the mouthpiece is about 1.5 inches wide, about 0.6 inches high andextends about 1.5 inches into the patient's mouth.
 40. The apparatus ofclaim 37 wherein the second portion of the mouthpiece has a length whichlimits loss of aerosolized solution.
 41. The apparatus of claim 37wherein the second portion of the mouthpiece has a length of about 8inches.
 42. A method comprising: applying an oscillating force to achest of a patient; positioning a mouthpiece in a mouth of the patientfor the patient to breathe through while the oscillating force isapplied to the chest; and collecting a sputum sample from the patientwhich is induced by the oscillating force and the mouthpiece.
 43. Themethod of claim 42 and further comprising: supplying a nebulizedsolution for the patient to inhale while applying the oscillating force.44. The method of claim 42 and further comprising: providing assessmentfollowing cytological evaluation of the sputum sample to determine thepresence of or the patient's risk for a pulmonary disorder.
 45. Themethod of claim 44 wherein the patient is classified as to risk of lungcancer based upon assessment.
 46. The method of claim 42 whereinpositioning the mouthpiece includes placing a first portion of themouthpiece into the patient's mouth to hold the patient's tonguedepressed.
 47. The method of claim 42 wherein the mouthpiece is sized topermit airflow velocities of greater than about 50 ml/cycle whileapplying the oscillating force.
 48. The method of claim 42 and furthercomprising: interrupting the applying of the oscillating force to permitthe patient to expectorate induced sputum into a sampling container. 49.The apparatus of claim 18 wherein the mouthpiece has a length adaptedfor limiting loss of an aerosolized solution.
 50. The apparatus of claim18 wherein the mouthpiece has a first portion adapted for locationinside the patient's mouth and a second portion adapted for locationoutside the patient's mouth, the second portion having a length of about8 inches.
 51. The apparatus of claim 18 wherein the mouthpiece is sizedto permit an airflow velocity of greater than 50 ml/cycle.
 52. Theapparatus of claim 18 wherein the mouthpiece is sized to permit anairflow velocity of about 90 ml/cycle.
 53. The apparatus of claim 18wherein the mouthpiece extends about 1.5 inches into the patient'smouth.
 54. The apparatus of claim 18 wherein the mouthpiece is sized tomaximize airflow velocity and minimize the loss of an aerosolizedsolution.
 55. The apparatus of claim 18 wherein a sputum sample isinduced by the force applied by the chest compression vest.